The mechanisms by which the heart hypertrophies in adaptation to a variety of stressful stimuli are not completely known. Regression of hypertrophy and regression of hypertrophy are the result of changes in net protein balance and could occur by alterations in the rates of protein synthesis, protein degradation, or both. The first objective of the proposed research is to further define changes in the rates of protein synthesis and of protein degradation which accompany the development and regression of cardiac hypertrophy. Inhalation of carbon monoxide will be used as the stimulus for cardiac hypertrophy. Carbon monoxide inhalation induces both left and right ventricular hypertrophy, probably by a volume overload mechanism, without the need for surgical intervention. Lysosomes and lysosomal enzymes have been implicated in the process of cardiac protein degradation. The second objective of this research is to correlate changes of the activity and availability of lysosomal proteinases with changes in proteolysis. Measurements of activity and availability (distribution in non-sedimentable vs. sedimentable fractions of tissue homogenates) of cathepsin B and D, two lysosomal proteolytic enzymes, beta-acetylglucosaminidage and acid phosphatase, lysosomal hydrolases and creatine kinase, a non-lysosomal enzyme, will be made. The use of a non-surgical model of cardiac hypertrophy will allow these measurements to be made free from the potentially obscuring influences of cardiac damage and repair induced by a surgical procedure.